Examination Date
Winter 3-12-2026
Degree
Dissertation
Degree Program
Physiology
Examination Committee
Jason Gardner, PhD; Janos Paloczi, PhD; Liz Simon, MVSc, PhD; Scott Edwards, PhD; Sarah Lindsey, PhD
Abstract
Alcohol use and nicotine vaping each pose significant cardiovascular risks, yet the combined biological impact of their concurrent use remains poorly understood despite high rates of co-use. Because these substances share overlapping mechanisms, including reactive oxygen species generation, inflammation, and autonomic activation, this dissertation sought to determine whether dual exposure produces additive or non-additive cardiovascular dysfunction.
A novel preclinical mouse model integrating chronic-plus-binge ethanol feeding with controlled nicotine vaping was developed. Male C57BL/6J mice (n=120) were assigned to six exposure groups varying by ethanol diet and aerosol type. Cardiovascular assessment included echocardiography, treadmill testing, pulse wave velocity, right and left ventricular catheterization, wire myography of the pulmonary artery and thoracic aorta, histology, RT-qPCR, western blotting, and quantitative label-free proteomics with pathway analysis.
Ethanol reduced survivability, impaired exercise capacity, increased liver and kidney mass, elevated CYP2E1, and induced hepatic lipid accumulation. Nicotine vaping decreased tibial length and independently impaired left ventricular systolic and diastolic function, including depressed pressure development and relaxation kinetics, reduced cardiac output, and altered electrocardiographic repolarization. Ethanol increased heart rate and diastolic blood pressure while reducing pulse pressure. Vascular studies revealed vessel-specific dysfunction: pulmonary arteries exhibited impaired smooth muscle responsiveness to nitric oxide donors, whereas thoracic aortas showed reduced α-adrenergic constriction and enhanced acetylcholine-mediated vasodilation with ethanol.
Proteomic profiling identified 3,144 ventricular proteins, revealing distinct exposure-specific and non-additive remodeling patterns. Dual nicotine-ethanol exposure altered 159 proteins and activated pathways involving mitochondrial quality control, lipid metabolic signaling, and oxidative stress defenses. Notably, dual exposure did not simply combine single-agent effects but generated unique proteomic signatures.
Collectively, these findings demonstrate that combined alcohol and nicotine vaping produce complex, interacting, and pathway-specific cardiovascular effects. The non-additive nature of dual exposure emphasizes the need for mechanistic and translational research targeting polysubstance cardiovascular risk.
Recommended Citation
Harris, Nicholas R., "CARDIOVASCULAR CONSEQUENCES OF POLYSUBSTANCE USE: DUAL CHRONIC PLUS BINGE ALCOHOL AND NICOTINE VAPE" (2026). School of Graduate Studies. 20.
https://digitalscholar.lsuhsc.edu/etd_sgs/20
Dissertation Report Form